Spectinomycin (MW 332 daltons) is the common name for an aminocyclitol antibiotic having the formula decahydro-4.alpha.,7,9-trihydroxy-2-methyl-6,8-bis(methylamino)-4H-pyrano[ 2,3-b][1,4]benzo-dioxin-4-one, (C.sub.14 H.sub.24 N.sub.2 O.sub.7), the structure of which is provided as Formula I below.
Spectinomycin functions as an antimicrobial, and in particular as an inhibitor of protein synthesis in the bacterial cell, having a site of action at the 30S ribosomal subunit. In humans, the compound has found particular application as an antimicrobial against N. gonorrhoeae. In veterinary and research applications, the compound has been found to be active in a variety of applications, including the treatment of diseases caused by infectious organisms susceptible to spectinomycin.
The compound can be isolated from the fermentation broth of the soil microbe Streptomyces spectabilis. Spectinomycin is available from Upjohn, under the brand name "Trobicin", in the form of a sterile powder for intramuscular injection. The powder is reconstituted with an accompanying sterile diluent (bacteriostatic water) prior to use, to achieve a final injectable suspension having a concentration of 400 mg/ml.
Sterile spectinomycin hydrochloride is said to exist in the form of the pentahydrated dihydrochloride salt. In its dihydrochloride pentahydrate form, the molecule is believed to exist as a ketone hydrate, rather than in the carbonyl form. Rigorous drying is necessary to remove the water and enable the infrared spectrum to display a ketone absorption band. See, for instance, "The Chemistry of Actinospcctacin", Wiley, P. F., Argoudelis, A. D., Hoeksema, H., J. Am. Chem. Soc. 85, 2652, (1963) and "Stereochemistry and Absolute Configuration of the Antibiotic Spectinomycin", Cochran, T. G., Abraham, D. J., Martin, L. L., J.C.S. Chem. Comm. 494, (1972).
When prepared for pharmaceutical applications in solution, rather than suspension form, such solutions are typically limited to spectinomycin concentrations of about 10% or less, by weight based on the weight of the solution. The maximum aqueous solubility of spectinomycin in the form of available salts such as the dihydrochloride is approximately 14% by weight.
The preferred concentration for veterinary use, however, can frequently be higher than 10%. As a result, the veterinarian often needs to use the compound in the form of an unstable suspension, thereby limiting its usefulness.
The ability to obtain more highly concentrated, stable aqueous compositions of spectinomycin would be of particular value to the veterinary professional.